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INTRODUCTION AND OBJECTIVES: Seroclearance of hepatitis B e antigen (HBeAg) is an important treatment goal for patients with chronic hepatitis B (CHB). This study developed a nomogram for predicting HBeAg seroclearance in CHB patients treated with nucleos(t)ide analogues (NAs). PATIENTS AND METHODS: Five hundred and sixty-nine CHB patients treated with NAs from two institutions between July 2016 to November 2021 were retrospectively included. One institution served as the training set (n = 374) and the other as the external validation set (n = 195). A predictive nomogram was established based on cox regression analysis. RESULTS: The overall HBeAg seroclearance rates were 27.3 and 21.5 % after the median follow-up of 100.2 weeks and 65.1 weeks in the training set and validation set, respectively. In the training set, baseline aspartate aminotransferase, gamma-glutamyl transpeptidase, HBeAg, and hepatitis B core antibody levels were independently associated with HBeAg seroclearance and were used to establish the HBEAg SeroClearance (ESC)-nomogram. The calibration curve revealed that the ESC-nomogram had a good agreement with actual observation. The ESC-nomogram showed relatively high accuracy for predicting 48 weeks, 96 weeks, and 144 weeks of HBeAg seroclearance in the training set (AUCs: 0.782, 0.734 and 0.671) and validation set (AUCs: 0.699, 0.718 and 0.689). The patients with high ESC-nomogram scores (≥ 79.51) had significantly higher cumulative incidence of HBeAg seroclearance and seroconversion than patients with low scores (< 79.51) in both sets (P < 0.01). CONCLUSIONS: The novel ESC-nomogram showed good performance for predicting antiviral efficacy in HBeAg-positive CHB patients with NAs treatment.
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Hepatite B Crônica , Humanos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/complicações , Antígenos E da Hepatite B , Antivirais/uso terapêutico , Estudos Retrospectivos , Nomogramas , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Resultado do Tratamento , DNA ViralRESUMO
Polyethylene (PE) is widely used, and it has caused serious environmental problems due to its difficult degradation. At present, the mechanism of PE degradation by microorganisms is not clear, and the related enzymes of PE degradation need to be further explored. In this study, Acinetobacter baumannii Rd-H2 was obtained from Rhizopertha dominica, which had certain degradation effect on PE plastic. The degradation performance of the strains was evaluated by weight loss rate, SEM, ATR/FTIR, WCA, and GPC. The multi-copper oxidase gene abMco, which may be one of the key genes for PE degradation, was analyzed and successfully expressed in E. coli. The laccase activity of the gene was determined, and the enzyme activity was up to 159.82 U/L. The optimum temperature and pH of the enzyme are 45 °C and 4.5 respectively. It shows good stability at 30-45 °C. Cu2+ can activate the enzyme. The abMCO was used to degrade polyethylene film, showing a good degradation effect, proving that the enzyme could be the key to degrading PE.
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Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: < 5%), and the concentrations of insulin and C-peptide were > 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.
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Doenças Autoimunes , Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Hipoglicemia , Doenças Autoimunes/diagnóstico , Peptídeo C/uso terapêutico , Coma , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/complicações , Cetoacidose Diabética/tratamento farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Anticorpos Anti-Insulina/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
ABSTRACT Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.
Los anticuerpos contra la insulina (AI) inducidos por la insulina exógena raramente causan hipoglucemia. No obstante, los autoanticuerpos contra la insulina (AIA) en el síndrome autoinmune de insulina (SAI) pueden causar hipoglucemia. Las manifestaciones típicas del SAI son la hipoglucemia en ayunas o posprandial, niveles elevados de insulina, la disminución del nivel de péptido C y AIA positivos. Presentamos un paciente hombre de 45 años con diabetes mellitus de tipo 1 (DMT1) tratado con análogos de insulina, que sufría comas hipoglucémicos recurrentes y cetoacidosis diabética (CAD). Sus síntomas fueron causados por la insulina exógena y fueron similares al SAI. La posible razón fue que la insulina exógena indujo AI. El título de AI era del 61,95% (Normal: 300 mU/L y < 0,02 nmol/L cuando se producía la hipoglucemia. Basados en sus síntomas clínicos y otros exámenes, se le diagnosticó hipoglucemia hiperinsulinémica causada por la AI. Sus síntomas mejoraron después de cambiar el régimen de insulina de lispro más insulina detemir a insulina humana recombinante (Gensulin R) y de empezar a tomar prednisona.
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Humanos , Masculino , Pessoa de Meia-Idade , Doenças Autoimunes/diagnóstico , Cetoacidose Diabética/complicações , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Peptídeo C/uso terapêutico , Coma , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Anticorpos Anti-Insulina/uso terapêuticoRESUMO
OBJECTIVE: Access to acute stroke unit (ASU) care is known to vary worldwide. We aimed to quantify regional variations in the various components of ASU care. METHOD: Secondary analysis of the Head Positioning in acute Stroke Trial (HeadPoST), an international, multicentre, cluster crossover trial of head-up versus head-down positioning in 11,093 acute stroke patients at 114 hospitals in 9 countries. Patients characteristics and 11 standard components of processes of care were described according to ASU admission within and across four economically-defined regional groups (Australia/UK, China [includes Taiwan], India/Sri Lanka, and South America [Brazil/Chile/Colombia]). Variations in process of ASU care estimates were obtained in hierarchical mixed models, with adjustment for study design and potential patient- and hospital-level confounders. RESULTS: Of 11,086 patients included in analyses, 59.7% (n = 6620) had an ASU admission. In China, India/Sri Lanka and South America, ASU patients were older, had greater neurological severity and more premorbid conditions than non-ASU patients. ASU patients were more likely to receive reperfusion therapy and multidisciplinary care within regions, but the components of care varied across regions. With Australia/UK as reference, patients in other regions had a lower probability of receiving reperfusion therapy, especially in India/Sri Lanka (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.12-0.63) and multidisciplinary care (mainly in formal dysphagia assessment, physiotherapy and occupational therapy). CONCLUSION: There is significant variation in the components of stroke care across economically-defined regions of the world. Ongoing efforts are required to reduce disparities and optimise health outcomes, especially in resource poor areas. CLINICAL TRIAL REGISTRATION: HeadPoST is registered at ClinicalTrials.gov (NCT02162017).
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Acidente Vascular Cerebral , Austrália , Brasil , Chile , China , Colômbia , Humanos , Índia , Qualidade da Assistência à Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , TaiwanRESUMO
Brucellosis, a zoonosis with worldwide distribution, is a systemic infection caused by bacteria of the genus Brucella. Meanwhile, brucellosis often causes complications, such as osteoarticular involvement, and spondylitis is the most prevalent and important clinical form. Here, is a case of cervical brucellar spondylitis causing incomplete limb paralysis in a middle-aged male. The diagnosis was based on clinical history, and supported by Brucella serology and magnetic resonance imaging. Quadruple antibacterial treatment continued for four weeks. In this case, the epidural abscess causing spinal cord compression resolved without surgery. In addition, the patient had recovered from most of the neurologic deficits.
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Brucelose/diagnóstico , Abscesso Epidural/etiologia , Paralisia/etiologia , Espondilite/diagnóstico , Brucelose/complicações , Vértebras Cervicais , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Espondilite/complicaçõesRESUMO
Abstract Brucellosis, a zoonosis with worldwide distribution, is a systemic infection caused by bacteria of the genus Brucella. Meanwhile, brucellosis often causes complications, such as osteoarticular involvement, and spondylitis is the most prevalent and important clinical form. Here, is a case of cervical brucellar spondylitis causing incomplete limb paralysis in a middle-aged male. The diagnosis was based on clinical history, and supported by Brucella serology and magnetic resonance imaging. Quadruple antibacterial treatment continued for four weeks. In this case, the epidural abscess causing spinal cord compression resolved without surgery. In addition, the patient had recovered from most of the neurologic deficits.
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Humanos , Masculino , Paralisia/etiologia , Espondilite/diagnóstico , Brucelose/diagnóstico , Abscesso Epidural/etiologia , Espondilite/complicações , Brucelose/complicações , Imageamento por Ressonância Magnética , Vértebras Cervicais , Pessoa de Meia-IdadeRESUMO
Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.
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Animais , Feminino , Humanos , Ratos , Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Nanotubos de Carbono , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Antineoplásicos/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Ratos Sprague-DawleyRESUMO
Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.
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Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Nanotubos de Carbono , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Animais , Antineoplásicos/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Ratos , Ratos Sprague-DawleyRESUMO
Molecular genetic confirmatory testing with polymerase chain reaction amplification is integral to neonatal hemoglobinopathy screening programs. In this study, we demonstrate applicability of polymerase chain reaction-based testing for the common deletions in blacks responsible for hereditary persistence of fetal hemoglobin. This approach will provide rapid diagnostic clarification in newborn screening follow-up.